a drug development company focusing on cell therapy …€¦ · translational medicine in car-t...

NASDAQ: CBMG

Cellular Biomedicine GroupA DRUG DEVELOPMENT COMPANY FOCUSING ON CELL THERAPY

“Meeting the Challenge of Delivering Cell

& Gene Therapy Products to Patients”

Yihong Yao, PhD, Chief Scientific Officer

CAR-TCR Summit, Boston

September 11, 2019

Safe Harbor

Statements in this presentation relating to plans, strategies, trends, specific activities or investments, and other statements that

are not descriptions of historical facts and may be forward-looking statements within the meaning of the Private Securities

Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities

Exchange Act of 1934, as amended. Forward-looking information is inherently subject to risks and uncertainties, and actual

results could differ materially from those currently anticipated due to a number of factors, which include those regarding our

ability to implement our plans, strategies and objectives for future operations, including our plan to configure part of our

Shanghai facility with GE Healthcare’s FlexFactory™ platform, our ability to execute on our obligations under the terms of our

licensing and collaboration arrangement with Novartis, our ability to execute on proposed new products, services or

development thereof, results of our clinical research and development, regulatory infrastructure governing cell therapy and

cellular biopharmaceuticals, our ability to enter into agreements with any necessary manufacturing, marketing and/or

distribution partners for purposes of commercialization, our ability to seek intellectual property rights for our product candidates,

competition in the industry in which we operate, overall market conditions, any statements or assumptions underlying any of the

foregoing and other risks detailed from time to time in CBMG’s reports filed with the Securities and Exchange Commission,

quarterly reports on form 10-Q, current reports on form 8-K and annual reports on form 10-K. Forward-looking statements may

be identified by terms such as "may," "will," "expects," "plans," "intends," "estimates," "potential," or "continue," or similar terms

or the negative of these terms. Although CBMG believes the expectations reflected in the forward-looking statements are

reasonable, they cannot guarantee that future results, levels of activity, performance or achievements will be obtained. CBMG

does not have any obligation to update these forward-looking statements other than as required by law.

This presentation is strictly intended to provide general information about our company and business. Neither this presentation

nor any part hereof constitutes an offer of securities.

CBMG Confidential

2

High Quality Clinical Results from Top Sites Globally

Key Objectives

Global R&D Capabilities

- Dynamic & Respected Advisory Board, R&D Centers in the U.S. and China

Best In Class CMC in China For Cell & Gene Therapy

- Research, Process Development, Commercial

Digital Platform Application for Manufacturing and Beyond

- Data >> Information >> Knowledge >> Therapeutics

Biotech Culture

- Talents >> Team >> Sustainable Success

3

CBMG: A Complete Solution for Cell Therapy in China and Eventually in the US

Pre-clinical Research

GMP Manufacture

QA/QC

IND Submission

Clinical Development

NMPA Filing

Translational Medicine (TM)

(Investigator initiated trial)

IIT

Early Safety & POC Readout

Positive Results

CBMG Confidential

4

Seasoned Research & Translational Medicine Teams

with Extensive Global Pharma Experience

Strong expertise in T cell immunology

and immuno-oncology

• CAR-T and TCR-T engineering

• TIL research

• Gene editing

• T cell modulation

CBMG Confidential

5

Translational Medicine in CAR-T Cell Therapy

• Safety/efficacy packages for IND filings to

NMPA

• Support clinical development:

• PK and PD assays

• Immunogenicity

• Understanding response or lack of

response, duration of response

• Putative early biomarkers to predict

efficacy and safety

• Disease indication selection and patient segmentation for CBMG clinical assets

CBMG Confidential

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Translational Medicine Guided Indication Selection

7

An Example of Real Time Delivery of PK/PD Information for an ALL Patient treated with CD19 CART

-3 0 4 7 10 14 21 24 28 30

102

103

104

105

106

107

0

2

4

6

8

10

0

10

CAR Copies

CD19+B cells

Days after Infusion

CA

R C

op

ies

(no

./u

g g

DN

A)

CD

19

+B

ce

lls（

%）

Visit

CD19+ Bone Marrow

Blast Cell by flow

cytometry

Baseline 8.6%

2w <10-4

4w <10-4

8w <10-4

12w <10-4

9

NGS Detected Minor Leukemic Clone in BM Biopsy of a MRD-CR ALL Patient 4 Weeks after CD19 CAR-T Treatment

A B1 bp difference between the clonotype

CDR3 sequences A and B

-TAC

In vitro efficacy study

In vivo efficacy study

Bio-distribution

study

Safety study

GLP toxicological

study

Safety/Efficacy Packages for IND Filings for CFDA

CBMG Confidential 10

CBMG: Immuno-Oncology Pipeline

CLL = chronic lymphocytic leukemia DLBCL = diffuse large B cell lymphoma NHL = non-Hodgkin lymphoma

SLL= small lymphocytic lymphoma MM = multiple myeloma NSCLC = non small cell lung cancer

HCC= hepatocellular carcinoma

CBMG Confidential

11

© 2019, Cellular Biomedicine Group, lnc.12

Early POC Readout in China Allows Speedy Decision Making

Large patient population allows speedy

enrollment without sacrificing the quality of

clinical trials

Investigator initiating trials (IIT) provide crucial,

quick POC readout, and allows speedy and

financially favorable key decision making

ASR, age-standardized rate

The 5 most commonly diagnosed

cancer types and age-standardized

incidence rate in 2018 in China

Cancer Communicationsvolume 39, Article number: 22 (2019)


High Quality Clinical Trial and Quality Assurance

• Highly experienced Pis and top 3 A hospitals in China

• All studies conducted to ICH-GCP

• Three levels of Q/A– Full-time Clinical Research Coordinator (CRC) embedded at every study site

– Twice monthly visit to site by CRA, focus on source data verification.

– Monthly visit to site by Clinical Research Operations Head/Medical Director of Oncology

– Site visits as required by CEO and Head of Development Strategy

• For all patients daily real-time reports to clinical management team monitoring

vital signs and any safety issues

• Risk minimization: ensure sites have capability and experience to manage

potential CRS/CANS* issues.

• Site refresher training on GCP and CRS management at all Site Initiation

Visits *Cell Associated Neurotoxicity Syndrome


Real-time Daily Patient Monitoring

• Daily contact with site to

assess progress of each

patient

• Particular focus on signs of

CRS/CANS*

• Constant monitoring by clinical

management team in Shanghai

• CAR-T experts in USA on hand

for consultation at any time.

*Cell Associated Neurotoxicity Syndrome

9/9/201915

Multiple Myeloma

• MM accounts for 1% of all cancers and ∼10% of all hematological malignancies1.

• The global incidence of multiple myeloma rose by 126% from 1990 to 2016. East Asia (China, North Korea, and Taiwan) saw incident cases of multiple myeloma jump by 262%, which was the largest increase among any of the 21 global regions 2

• China is the top 2 countries with the most incident cases and deaths(16 537; 95% UI, 14 094-18 617] incident cases and 10 363 [95% UI, 9079-11 898] deaths)2

1.Moreau P et al., Annals of Oncology 24 (Supplement 6): vi133–vi137, 2013

2..Cowan AJ et al., JAMA Oncol. 2018;4(9):1221-1227.

© 2019, Cellular Biomedicine Group, lnc.

Multiple myeloma

Age-Standardized Incidence Rate of

Multiple Myeloma 2

CBMG Anti-BCMA CAR-T in vitro Activity is Comparable to Industry Leading Candidate

BCMA-CAR expression

NT

Positive

con

trol

CBM

.BCM

A

0

500

1000

1500

200010000

20000

30000

40000T cell only

K562

K562-BCMA+E7

IFN

-γ (pg/m

l)

CD137 up-regulation

IFN-g release

CBMG Confidential16

CBMG Anti-BCMA CAR-T Showed Good in vitro Anti-tumor Activity


D a y s p o s t in je c tio n

Su

rv

iva

l(%

)

0 2 0 4 0 6 0

0

2 0

4 0

6 0

8 0

1 0 0

C o n tro l

T c e lls

C -C A R 0 8 8 2 .5 x1 06c e lls

C -C A R 0 8 8 5 x 1 06c e lls

C -C A R 0 8 8 1 0 x1 06c e lls

*

D a y s p o s t in je c tio n

Tu

mo

r V

olu

me

(m

m3

)

0 2 0 4 0 6 0

0

5 0 0 0

1 0 0 0 0

1 5 0 0 0 C o n tro l

T c e lls

C -C A R 0 8 8 2 .5 x1 06c e lls

C -C A R 0 8 8 5 x 1 06c e lls

C -C A R 0 8 8 1 0 x1 06c e lls

C-CAR088 (from CBM.BCMA CAR-T standard manufacture) showed good anti-tumor

activity in animal studies (RPMI-8226 tumor model).

• IIT was initiated early this year

• 3+3 dose escalation study in second cohort

• Multi center trials

CBMG Anti-BCMA CAR-T Showed Dose Dependent in vivo Anti-tumor Activity


9/9/201919

• HCC is the 4th most common cancer in

China1 and more than 50% of new HCC

cases world-wide are in China1,2.

• 466K new HCC cases each year and the

mortality is around 422K annually in China1.

• Current systemic treatments for

unresectable HCC in China is not ideal:

• First Line: Sorafenib, FOLFOX 4 ; Lenvatinib:

likely to be approved in 2018

• Second Line: Regofenib

1.Chen et al. CA Cancer J Clin 2016;66:155-132; 2.Bray F et al. CA Cancer J Clin 2018: 68:394-424

Hepatocellular Carcinoma (HCC) in China


DE novo TCR Discovery Technology Platform

Lentivector prime & peptide boost immunization to identify TCRs with high diversity


Developing Promising TCRs Against AFP

• Identified AFP specific

TILs by immunizing HLA-

A2 transgenic AAD mice

with AFP158-166(FMNKFIYEI)

Zhu et al. Hepatology 2018

• Selectively cloned nine

independent TCRs from

AFP specific TILs

• Exclusive global IP

secured

• IIT for AFP TCR-T has

obtained IRB approval

and will start recruiting

patients in China next

monthCBMG Confidential 21

Human AFP TCR-T Specifically Recognize HLA-A2+ Presented Epitope in vitro and in vivo

in vivo anti-tumor activity of TCR2


BCMA Specific CARsNo Reactivity of AFP TCR Detected to Human HLA-A2 Primary Cells from Essential Organs

Hep

atoc

yte

1

Hep

atoc

yte

2a

Hep

atoc

yte

2b

Hep

G2

Huh

7

Hep

atoc

yte

1

Hep

atoc

yte

2a

Hep

atoc

yte

2b

Hep

G2

Huh

7

0

2000

4000

20000

40000

60000

80000

UT TCR055

Donor A Donor B

IFNg

(ng/m

L)

UT TCR055 UT TCR055

Donor A Donor B

4-1

BB

CD8

Source 1

Source 2_a

Source 2_b

Huh7

HepG2

Normal primary

HLA-A2+

Hepatocytes

Liver

cancer

line

(HLA-A2-AFP+)

(HLA-A2+AFP+)

Cell type HLA-A2 IFN-g release

Hepatocyte + No

Neuron + No

Astrocyte + No

Cardiomyocyte + No

Lung + No

Kidney + No

Endothelial + NoCBMG Confidential 23

No Allo-reactivity of AFP TCR Detected for >90% Chinese HLA Serotypes

1332-8

265

1333-8

280

1413-1

218

AM

AI

DU

G150

FH

43

FH

69

FH

72

KA

S011

KT

12

KT

14

LA

TIF

LK

T3

LU

Y

MA

NIK

A

T7526

TA

B

TU

BO

Huh7

HepG

2

0

10000

20000

30000

40000

50000

60000

UT TCR055

IFNg

(pg/m

L)

1332-8

265

1333-8

280

1413-1

218

AM

AI

DU

G150

FH

43

FH

69

FH

72

KA

S011

KT

12

KT

14

LA

TIF

LK

T3

LU

Y

MA

NIK

A

T7526

TA

B

TU

BO

Huh7

HepG

2

0

5000

10000

15000

UT TCR055

IFNg

(pg/m

L)

97.83% 89.13% 99.89% 100%cum.%

100% 89.24% 100% 100%cum.%

Ranked HLA subtypes within the Chinese population

tested not tested

No above background IFN-g was detected when AFP TCR055 T

cells were co-cultured with 24 EBV-transformed human B cell lines

covering the majority of HLA serotypes within the Chinese

population, only 18 lines were shown above.

CBMG Confidential

24

Development of TIL as a Treatment for Immunogenic Solid Cancers

• TIL therapy, a potent and safe treatment

for immunogenic cancers

• Multiple TIL manufacturing processes

available

• Traditional TIL (NCI)

• Young TIL (fast TIL)

• Neoantigen-reactive TIL (NCI, licensed by

CBMG)

• Top potential indications in the US and

China

• Non small cell lung cancer, head and neck

cancer, cervical cancer, ovarian cancer,

stomach cancer

• Potential of combination therapy with

immune checkpoint inhibitors

Somatic mutation burden by cancer

Somatic mutation burden by cancer

Nature Biotechnology 34, 1019–1024 (2016)



Producing TIL Enriched with Neoantigen-reactive

Cells for Clinical Use

IL-2 TIL

•Isolating 4-1BB+ T cells from fresh tumor

digest, which are enriched with

neoantigen-reactive cells

•Growing isolated cells for rapid expansion

(REP)

•Expanding neoantigen-reactive TIL to

>5e9 cells for clinical use

•NCI granted CBMG worldwide license to

develop, manufacture and commercialize

the neoantigen-reactive TIL to treat a

variety of cancer indications

9/9/2019


27

Lung cancer remains the leading cause of cancer-related mortality in the world1.

Lung cancer new case and mortality in US, china, worldwide 20182

Non-small cell lung cancer (NSCLC) is the most common type of lung

cancer and represent about 85% of lung cancer cases3

Currently, available cares of NSCLC include chemotherapy, targeted therapy and

immune checkpoint pathway inhibitors

1Feng et al. Cancer Commun (2019) 39:22 2 Bray F et al. CA Cancer J Clin. 2018;68(6):394–4243Duma, N et al. Mayo Clinic Proceedings, (2019). 94(8), 1623–1640

Non-Small Cell Lung Cancer

CBMG Confidential28

Preliminary NSCLC TIL Therapy Results

Courtesy from Dr. Antonia, AACR 2019

• NSCLC TIL could be expanded

and infused in 91% of patients.

• Despite rapid progression on

nivolumab, decreases in tumor

size were observed in PD-1

refractory population with TIL.

• 10 patient received TIL

• 3 PR and 1 pathology CR

• 4 patients remain on treatment 6-

15 months

Best Overall Change in Target Lesions

Pre-TIL Post-TIL

1 4 0 5 1 3 1 2 1 5 0 4 0 1 0 3 0 8 0 2 1 6 0 9 0 7

- 8 0

- 6 0

- 4 0

- 2 0

0

2 0

4 0

6 0

S u b j e c t I D

Ch

an

ge

fr

om

ba

se

lin

e (

%)

*

* P D d u e t o n e w l e s i o n s a n d / o r n o n - t a r g e t p r o g r e s s i o n

P D - L 1 T P S 2 0 %

**

P D - L 1 T P S > 2 0 %**

* **

1 4 0 5 1 3 1 2 1 5 0 4 0 1 0 3 0 8 0 2 1 6 0 9 0 7

- 8 0

- 6 0

- 4 0

- 2 0

0

2 0

4 0

6 0

S u b j e c t I DC

ha

ng

e f

ro

m b

as

eli

ne

(%

)

*


P D - L 1 T P S 2 0 %

**

P D - L 1 T P S > 2 0 %**

* **

1 4 0 5 1 3 1 2 1 5 0 4 0 1 0 3 0 8 0 2 1 6 0 9 0 7

- 8 0

- 6 0

- 4 0

- 2 0

0

2 0

4 0

6 0

S u b j e c t I D

Ch

an

ge

fr

om

ba

se

lin

e (

%)

*


P D - L 1 T P S 2 0 %

**

P D - L 1 T P S > 2 0 %**

* **

T I L , I L 2

Most patients had rapid progression on nivolumab, then some tumor decrease after Cy/Flu/TIL/IL2

1 5 1 4 0 3 1 3 0 1 0 8 0 4 0 5 0 2 1 6

- 6 0

- 4 0

- 2 0

0

2 0

4 0

6 0

S u b j e c t I D

Ch

an

ge

fr

om

ba

se

lin

e (

%)

L e g e n d

* * *

Courtesy from Dr. Antonia, AACR 2019


Summary

• CBMG is well positioned to deliver POC under IITs in China for CBMG assets

• POC for anti-BCMA CAR is expected in Q4 2019. POC for other assets will soon follow. Based on clinical results, decision to be made whether to initiate clinical trials of these two products in the US

• CBMG plans to initiate TIL trials in the US with highly influential PIs in top medical centers.

CBMG Confidential

30

Saving Life

Revitalizing Life

www.cellbiomedgroup.com

-21d -5d -4d -3d

ICF

Screening

D0 D4 D7 D10 W2 W3 W4 W8 W12 W16 W20 M6 M9 M12

Apheresis C-CAR088

Manufacturing QC

r/r MM Flu： 30mg/m2/d

Cy： 300mg/m2/dC-CAR088

infusion

Baseline

assessment

-7d

CBMG

3+3 Dose Escalation

1x106/Kg 3x106/Kg 6x106/Kg 9x106/Kg( TBD)

Initiate expansion cohort to explore optimal dose

• Safety Assessment： Rate of dose limiting toxicities; Incidence and severity of treatment-emergent

adverse events(CTCAE V5.0)

• Efficacy Assessment： IMWG ORR;DOR; PFS; OS

• Exploratory：CAR-T expansion and persistence

Key Eligibility Criteria：• 18-75 years of age

• MM cells express BCMA

• Must have measurable MM

• ≥ 3 prior lines of therapy for

MM, having received

treatment PI and IMiD

• Must have adequate

hepatic, renal, cardiac and

hematopoietic function


Phase I Study in Relapsed and Resistant

Multiple Myeloma

a drug development company focusing on cell therapy …€¦ · translational medicine in car-t...

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